tbuckley/cabot-search huggingface dataset:
POS0409 INTESTINAL HIF1α EXPRESSION PROTECTS AGAINST EPITHELIAL CELL DEATH IN ARTHRITIS
Authors: P. Lyu, J. Wen, I. Stolzer, A. Giessl, R. Song, X. Meng, S. Cao, C. Günther, G. Schett, A. Bozec
Journal: Annals of the Rheumatic Diseases (2022)

Background While a so-called gut-joint axis is supported by many clinical observations, the current knowledge on such axis is mostly confined to descriptive and correlative data, e.g. showing the microbiota changes are associated with arthritis. In contrast, mechanistic data on how molecular changes in the intestinal epithelium influence the development of arthritis are scarce. Objectives To investigate, whether the mucosal barrier in the intestine dependent of the epithelial cell survival maintenance, influences the development of arthritis. Methods Intestinal hypoxia inducible factor (HIF)-1α expression was assessed before, at onset and during experimental arthritis and human rheumatoid arthritis (RA). Intestinal epithelial cell-specific HIF1α conditional knock-out mice were generated (HIF1α ΔIEC ) and subjected to collagen-induced arthritis (CIA). Clinical and histological courses of arthritis were recorded, and T and B cell subsets were analyzed in the gut and secondary lymphatic organs, and intestinal epithelial cells were subjected to molecular mRNA sequencing in HIF1α ΔIEC and littermate control mice. Furthermore, pharmacologic HIF1α stabilization by PHD inhibitor was used for the treatment of arthritis. Results Intestinal HIF1α expression peaked at onset and remained high in experimental arthritis and RA. Conditionally deletion of HIF1α in gut epithelial cells strongly exacerbate arthritis and was associated with increased gut epithelial cell death, intestinal and lymphatic Th1 and Th17 activation. Mechanistically, HIF1α inhibits the transcription of necroptotic and apoptotic markers, which leads to a defect in the intestinal barrier integrity. Furthermore, treatment with HIF1α stabilization reinforced the gut epithelial cell survival and inhibited arthritis. Conclusion These findings show that the HIF1α regulating epithelial cells survival is critical for the breakdown of the intestinal barrier function in arthritis highlighting the functional link between intestinal homeostasis and arthritis. Disclosure of Interests None declared.
AB0950 Detection of asymptomatic entheseal involvement in patients with psoriasis: A case-control ultrasound study
Authors: R. Ben Aissa, S. Boussaid, S. Rekik, S. Rahmouni, S. Jemmali, H. Ajlani, H. Srairi Sahli, M. Elleuch, A. Souissi, M. Mokni
Journal: Annals of the Rheumatic Diseases (2022)

Background Enthesopathy is one of the major features of psoriatic arthritis (PsA). The clinical screening for enthesopathies and synovitis in patients with psoriasis is nonspecific during the subclinical phase. Ultrasonography (US) has already demonstrated its ability to study entheses and joints in early stages of PsA. Objectives To evaluate the prevalence of ultrasonographic subclinical synovitis and enthesopathies in psoriasis patients with no clinical evidence of PsA compared with controls. Methods A cross-sectional study conducted on 40 patients with psoriasis and 40 healthy sex- and age- matched controls. The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) were used to evaluate entheseal involvement. US examination of 18 joints (wrists, metacarpophalangeal, and proximal interphalangeal joints) was performed along with 22 entheseal sites (deep flexor of the fingers, lateral epincondyle, triceps, quadriceps, patellar and calcaneal tendons and plantar fascia). Inflammatory-score (thickening, hypoechogenocity, bursitis and Doppler signal) and damage-score (calcifications, enthesophytes and erosions) were calculated (0= absent, 1=present for each abnormality). A total-score was obtained by adding these two scores. Results The mean age of psoriatic patients 51,90±15,90 [19 -76] and the sex ratio of males to females was 3:2. US synovitis were more frequent in psoriatic patients 7/1040 (0,68%) than in controls 3/1040 (0,29%) but this was not significant (p= 0,420). Patients with psoriasis had more US enthesopathies 37 (92,5%) comparing to controls 16 (40%) (p &lt; 0,001). The total number of enthesopathies was higher in the psoriatic group 184/880 (20,90%) comparing to controls 42/880 (4,78%) (p &lt; 0,001). Entheses with more US abnormalities in the psoriasis group comparing to controls were deep flexor tendons of the fingers entheses (p&lt;0,001), distal patellar tendon entheses (p&lt;0,001) and calcaneal tendon entheses (p&lt;0,001). LEI and SPARCC scores were positively correlated to higher number of US enthesopathies (p=0,046, p=0,006). SPARCC was positively correlated to inflammatory-score and damage-score (p=0,009, p=0,024). The mean C-reactive protein level was higher in psoriatic arthritis 5,77±10,10 mg/L than in controls 2,15±3,26mg/L (p=0,037). Conclusion Our results confirm that US enthesopathies and synovitis are more frequent in patients with psoriasis comparing to healthy population. The US screening for subclinical enthesopathies should be the object of longitudinal investigations to define its value in predicting the clinical onset of PsA. Disclosure of Interests None declared
AB0919 Psoriatic arthritis: factors associated with the use of biotherapy
Authors: S. Sayouri, N. Akasbi, H. Bourkhime, I. El Mezouar, T. Harzy
Journal: Annals of the Rheumatic Diseases (2022)

Background The use of biological treatment in psoriatic arthritis has revolutionized its management with both joint and skin efficacy [1]. Objectives The goal of our study was to evaluate the use of biological treatment in these patients and to assess the factors associated with it. Methods Retrospective study conducted within the rheumatology department of the University Hospital of Fez. Patients were recruited from January 2011 to January 2021. We included patients with psoriatic arthritis according to CASPAR criteria and assessed the use of biotherapy as well as the epidemiological, clinical and biological factors associated with it. Results There were a total of 98 patients with psoriatic arthritis, 21 of whom had been put on biological treatment. Of the total of 21 patients, there were 42.9% women and 57.1% men, the average age was 51.1 (± 9.92) years. 20% of patients had a history of tuberculosis, 14.3% had diabetes, 10% had hypertension and 30% had dyslipidemia. 60% of patients had an inflammatory syndrome, 73% had radiographic sacroiliitis and 63.2% had functional repercussions. In bivariate analysis, the value of the initial C-reactive protein CRP (p = 0.04), the initial disease activity score DAS 28 CRP (p = 0.0001) and the value of the initial erythrocyte sedimentation rate ESR (p = 0.02) were significantly associated with the use of biotherapy, there was no significant association with the other parameters. In multivariate analysis, no factor was significant. Conclusion An active psoriatic arthritis predicts the prescription of a biological treatment, other studies with a larger sample would be necessary to confirm our results. References [1]Julien Schemoul et al, Stratégies thérapeutiques dans le rhumatisme psoriasique, Revue du rhumatisme (2017)-4907. Disclosure of Interests None declared
An introduction to spatial transcriptomics for biomedical research
Authors: Cameron G. Williams, Hyun Jae Lee, Takahiro Asatsuma, Roser Vento-Tormo, Ashraful Haque
Journal: Genome Medicine (2022)

Abstract Single-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact and viable from tissue. This has precluded many cell types from study and largely destroys the spatial context that could otherwise inform analyses of cell identity and function. An increasing number of commercially available platforms now facilitate spatially resolved, high-dimensional assessment of gene transcription, known as ‘spatial transcriptomics’. Here, we introduce different classes of method, which either record the locations of hybridized mRNA molecules in tissue, image the positions of cells themselves prior to assessment, or employ spatial arrays of mRNA probes of pre-determined location. We review sizes of tissue area that can be assessed, their spatial resolution, and the number and types of genes that can be profiled. We discuss if tissue preservation influences choice of platform, and provide guidance on whether specific platforms may be better suited to discovery screens or hypothesis testing. Finally, we introduce bioinformatic methods for analysing spatial transcriptomic data, including pre-processing, integration with existing scRNA-seq data, and inference of cell-cell interactions. Spatial -omics methods are already improving our understanding of human tissues in research, diagnostic, and therapeutic settings. To build upon these recent advancements, we provide entry-level guidance for those seeking to employ spatial transcriptomics in their own biomedical research.
AB1067 ASYMPTOMATIC HYPERURICEMIA AND ASSOCIATED FACTORS IN MALE PATIENTS VISITED HANOI MEDICAL UNIVERSITY HOSPITAL
Authors: T. Phạm, H. T. Pham, T. H. Pham, G. Trần, T. Nguyễn, T. Đỗ
Journal: Annals of the Rheumatic Diseases (2022)

Background Asymptomatic hyperuricemia prevalence in Vietnamese men has rose over the past several years. This leads to gout and increase cardiovascular risk. Objectives To assess the prevalence of asymptomatic hyperuricemia and associated factors in male patients who had medical check-ups in Hanoi Medical University Hospital. Methods All asymptomatic hyperuricemia male patients over 18 years old, had medical check-ups in outpatient clinics from January 2020 to May 2021. Exclude criteria included patients having medicine which affected serum uric acid (allopurinol, probenecid, sulfinpyrazone, salicylate, phenylbutazone, ascorbic acid, ethambutol, pyrazinamide, ect.), had acute diseases, diabetes type 1, chronic kidney disease and malignancies. All patients were tested for serum uric acid, total Cholesterol, Triglyceride, HDL-C, LDL-C and fasting serum glucose using Roche Cobas 6000 analyzer. Age, body mass index, alcohol consuming, physical activities and comorbidities were identified. Results 798 male patients over 18 years old were included in the study. Mean age was 39.5 ± 11.2, overweight and obesity rate was 31.5% and 29.8%, respectively. 41.4% patients had hyperuricemia with mean serum uric acid was 405.2 ± 81.2 μmol/l (highest was 820 μmol/l). We found that the factors associated to hyperuricemia in men were: the presence of hypertension (OR 1.64, 95% CI 1.1 -2.34), dyslipidemia (OR 2.37, 95% CI 1.73-3.24) and alcohol consuming (OR 2.16, 95% Cl 1.6-2.8). We did not find association between smoking, physical activities, impaired glucose tolerance with hyperuricemia. Conclusion Alcohol consuming, dyslipidemia and hypertension were associated with higher risk of incident asymptomatic hyperuricemia in Vietnamese men. Disclosure of Interests None declared
AB0876 Can ultrasonographic peripheral enthesitis mirror spinal radiographic abnormalities and other disease parameters in patients radiographic axial SpA?
Authors: A. Moshrif, M. I. Abdelkareem, S. Rashad, A. Negm, A. Mosallam, H. Bassiouni
Journal: Annals of the Rheumatic Diseases (2022)

Background Although enthesitis is the hallmark of spondyloarthritides, the association between peripheral enthesitis, radiographic spinal affection and disease assessment parameters is still underestimated. Objectives In this cross-sectional prospective study, we aimed to evaluate the relation of US pattern of peripheral enthesitis with the spinal radiographic changes and other disease parameters in patients with radiographic axial spondyloarthritis (SpA). Methods Fifty-eight patients with radiographic axial SpA (ASAS criteria) were studied for the presence and pattern of peripheral lower limb enthesitis according to the Outcome Measures in Rheumatology (OMERACT) US definitions: Achilles tendon, plantar fascia, proximal and distal patellar ligaments, and quadriceps tendon insertions. The findings then were correlated with the radiographic spinal abnormalities, Bath AS radiographic index (BASRI), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), and Bath AS metrology index (BASMI) together with the HLA-B27 status and inflammatory markers using Spearmann rho correlation co-efficient. Results The mean age was 37.96 (±13.1) years, 75.86% were males. Thirty-six patients (62%) had US enthesitis (USE) with a mean age of 39.2 (±12.8). HLA-B27 was positive in 61% of patients with USE and 54.5% in those without. There was no difference between patients with and without USE regarding the disease duration, age at onset but those with USE showed less diagnostic delay (p = 0.03). Clinical enthesitis and peripheral arthritis were more frequent in those with USE (50% vs 22.7% and 25% vs 13.6% respectively). No statistical significant difference has been found between the inflammatory, structural and total scores of USE and BASRI, BASFI and BASDAI (p &gt; 0.05). No correlation could be detected between BASRI and USE scores (rs= 0.12, p =0.45 for inflammatory, rs=0.25, p=0.11 for structural and rs=0.18, p=0.28 for total score). There was a positive correlation between BASMI and both inflammatory and total scores of USE (rs= 0.485, p=0.003). No significant association between BASDAI, CRP or ESR and USE scores. Conclusion Ultrasonographic peripheral entheseal abnormalities couldn’t reflect the spinal radiographic changes or disease assessment parameters in patients with radiographic axial SpA. However, these results can be considered preliminary and more studies on wider scales are needed to support our findings. Disclosure of Interests Abdelhfeez Moshrif Speakers bureau: Amgen, Jansen, Novartis, Mohamed Ismail Abdelkareem Speakers bureau: Abbvie, Jansen, Novartis and Organon, Sonya Rashad: None declared, Ahmed Negm: None declared, Ahmed Mosallam Speakers bureau: Amgen, Pfizer and Novartis, Hassan Bassiouni Speakers bureau: Abbvie, Jansen, Novartis, and MSD
Electronic Monitoring of Patient-Reported Outcomes—Ready for Prime Time?
Authors: Ana I. Velazquez, Narjust Florez
Journal: JAMA Oncology (2022)

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[18F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial
Authors: Abby Douglas, Karin Thursky, Timothy Spelman, Jeff Szer, Ashish Bajel, Simon Harrison, Shio Yen Tio, Olivia Bupha-Intr, Michelle Tew, Leon Worth, Benjamin Teh, Lynette Chee, Ashley Ng, Dennis Carney, Amit Khot, Gabrielle Haeusler, Michelle Yong, Jason Trubiano, Sharon Chen, Rodney Hicks, David Ritchie, Monica Slavin
Journal: The Lancet Haematology (2022)
AB1352 VALIDATING DIAGNOSTIC GCA ULTRASONOGRAPHY SKILLS AGAINST AN EXPERT SONOGRAPHER
Authors: F. Coath, C. Mukhtyar
Journal: Annals of the Rheumatic Diseases (2022)

Background Ultrasonography has become the recommended first line investigation for suspected giant cell arteritis (GCA). However, it is still not yet widely available in the UK due to a paucity of skilled rheumatologists. Effective training programmes have been developed, but subsequent hands-on practice is needed to become truly proficient. There is no consensus on the logistics of gaining the ‘appropriate’ level of skill. Objectives This project demonstrates a potential mechanism for validation against an expert sonographer. Methods Over a 6-month period, 12 scans of patients referred with suspected GCA were sequentially performed by first a trainee (FC) and then an expert sonographer (CM) on the same day. FC had theoretical knowledge and supervised practical experience but had not scanned independently prior to this project. CM has performed &gt;1000 scans. 6 vascular territories considered to be the core GCA US data set (common, frontal and parietal branches of the superficial temporal artery, and the 1 st , 2 nd and 3 rd part of the axillary artery) were marked as either ‘normal’ or ‘halo’. CM was blinded to FC’s results. Inter-observer reliability was calculated for all vascular territories using Cohen’s kappa. Results A total of 144 vascular territories were scanned in 12 patients. Table 1 details the inter-observer variation, with a near perfect level of agreement demonstrated, kappa=0.90 (95% CI 0.83 – 0.98). Table 1. Matrix of inter-observer variation for all vascular territories in 12 patients, k=0.90 (95% CI 0.83 – 0.98) FC positive FC negative Total CM positive 48 4 50 CM negative 2 90 92 Total 50 94 Conclusion This is the first study that demonstrates a mechanism for validation of ultrasonography skills which will allow GCA US to become a feasible reality in clinical practice. This project demonstrates that after acquiring supervised training, near perfect levels of agreement can be arrived between a trainee and expert. Disclosure of Interests None declared
AB1356 QUANTITATIVE ANALYSIS BY SODIUM AND PROTON BASED 3-TESLA MR IMAGING OF THE ACHILLES TENDON
Authors: A. Müller-Lutz, B. Kamp, L. Klein-Schmeink, S. Tsiami, M. Frenken, A. Nagel, X. Baraliakos, P. Sewerin
Journal: Annals of the Rheumatic Diseases (2022)

Background Decrease of proteoglycan is the initiating stage of post-inflammatory tissue degradation. Sodium MRI is promising great potential for identification and monitoring of proteoglycan changes in tendons and cartilage associated with inflammatory and degenerative musculoskeletal diseases, where the Achilles tendon is frequently affected. Objectives Proof-of-concept study to examine the usage of sodium MRI in quantifying sodium concentrations in the Achilles tendon in healthy volunteers. Methods Sodium ( 23 Na) MR imaging of the Achilles tendon together with established proton ( 1 H) MRI sequences were performed in 10 healthy volunteers (6 males, 4 females, age 29 ± 9 years) using a dual-tuned 23 Na/ 1 H surface coil (RAPID Biomedical GmbH, Würzburg-Rimpar, Germany). Imaging was performed using a 3D density adapted radial sequence [1] providing sufficient signal-to-noise ratio for sodium imaging. Reference tubes on the backside of the coil were used to enable assessment of sodium concentration from sodium signal-to-noise ratio maps. Sodium concentrations were determined for tendon insertion into calcaneus bone (INS), middle portion of the tendon (MID) and muscle-tendon junction (MTJ) and for the whole Achilles tendon. Statistical differences were analysed by Wilcoxon test. Results Sodium concentrations c [mM] of the Achilles tendon could be quantified in all 10 (exemplary selected volunteer is shown in Figure 1). Significantly higher sodium concentrations were obtained in INS compared to MID (p=0.002) and MTJ (p=0.002) and in MID compared to MTJ (p=0.037). The average sodium concentration of the whole Achilles tendon was 57.23±17.69 mM with only minor outliers in this healthy population. Figure 1. Sodium concentrations of the Achilles tendon. Highest sodium concentrations c(mM) were observed at the tendon insertion into calcaneus bone (INS), whereas lower concentrations were measured in the middle portion of the tendon (MID) and muscle-tendon junction (MTJ). Conclusion Performance of quantitative sodium imaging of the Achilles tendon in a high-field MRI machine is feasible for assessing sodium concentrations, a surrogate biomarker for proteoglycan content. Molecular MR studies investigating changes in the proteoglycan content of the Achilles tendon in patients with inflammatory and degenerative musculoskeletal diseases could support early diagnosis or therapy monitoring in the future. References [1]Nagel et al. Magn Reson Med (2009) 62(6):1565-73. DOI: 10.1002/mrm.22157 Disclosure of Interests None declared
POS1341 EVALUATION OF DAMAGE CAUSED BY SEPTAL PANNICULITIS ASSOCIATED WITH ACUTE SARCOIDOSIS
Authors: O. Egorova, G. Tarasova
Journal: Annals of the Rheumatic Diseases (2022)

Background Joint involvement in combination with septal panniculitis, erythema nodosum (EN), febrile reaction, and intrathoracic lymphadenopathy is the criteria for acute sarcoidosis (Löfgren’s syndrome, LS) – a granulomatous multisystem inflammatory disease of unknown etiology. Objectives to develop an index of damage caused by septal panniculitis for express-assessment of the X-ray stage of LS. Methods We examined 142 patients (31 men and 111 women) in case of EN associated with LS, average age 39.3±11.1 years. All patients underwent a comprehensive clinical, laboratory and instrumental examination, including ultrasound of the joints and computed tomography (СТ) of the chest organs. Results In 96% of cases, widespread EN was detected, which correlated with the level of CRP (p=0.006; r=0.38). In 124 patients (87%) there were signs of joint damage with predominantly periarticular changes in the area of ankle joints. The relationship between the duration of the articular syndrome and the duration of inflammatory changes in the subcutaneous tissue and the number of nodes was registered (p=0.02; r=0.45). The level of CRP had a significant direct correlation with the number of nodes (p=0.008; r=0.29) and the severity of articular syndrome (p=0.003; r=0.29). An elevated level of angiotensin-converting enzyme was detected in 97 patients (78%). The assessment of the probable radiological stage (c) of LS was performed according to the formula obtained using step-by-step discriminant analysis: с= 1,06*Х1 + 0,98 *Х2 + 5,21*А+ 1,68*CRP X1 – the number of sides of the lower/upper limbs with the detected diffuse lesions of the skin and subcutaneous fat; X2 – the number of erymatous nodes (or induration); A – the number of arthritis; CRP – concentration of C-reactive protein in absolute values. The value of c≤28.72 indicated x-ray Stage 0; 28.72˂c&lt;109.02 – x-ray Stage I, с ≥109.02 – x-ray Stage II of the LS of the chest organs. The developed technique made it possible to determine Stage I of LS in 69% of cases and Stage II in 15% of cases, which was confirmed by CT of the lungs. For the selected total value of the discriminant function of 3.984, the sensitivity is 79%, the specificity is 96%. Conclusion The developed assessment is a low-cost, affordable and fast way to assess the verification of the X-ray stage of LS at any stage of the disease, which contributes to the immediate prescription of adequate therapy. Disclosure of Interests None declared